1. Field of the Invention
This invention relates to a surgical cement, also known as bone cement or bioresorbable implantation material, and its process of formation. The cements of this invention are formed from calcium alkali phosphate ceramics and acidic citrate setting reagents, which when combined with an aqueous solution form a moldable paste having high biocompatibility. The paste is easy to manipulate and reaches neutral pH or higher shortly after hardening. The resulting cements are useful in orthopedic and maxillofacial surgeries and in dental applications.
2. Description of the Prior Art
In the last two decades, many artificial hard tissue implant materials have been made. Since the major inorganic component of human hard tissue (e.g. bone, teeth) is a calcium phosphate compound, which is biological apatite, hydroxyapatite and other calcium phosphate ceramics were logically selected for hard tissue implant materials.
Most of the previous calcium phosphate cements developed used hydroxyapatite or tricalcium phosphate as the cementing ceramic and phosphoric acid, bifunctional organic acids or other polyfunctional organic acids as setting reagents. These cements are normally very acidic in nature and take a very long time to reach neutral pH. After implantation, these cements may cause irritation and inflammatory reactions.
Biocompatibility has been the limiting factor in successful applications of implant materials. The most successful artificial implant materials to achieve the excellent biocompatibility have been hydroxyapatite, bioglass.sup.1, and other calcium phosphate ceramics. Hydroxyapatite and .beta.-tricalcium phosphate ceramics and calcium phosphate containing glass have been extensively studied. Clinical studies confirmed that most of the calcium phosphate ceramics such as hydroxyapatite, tricalcium phosphate, tetracalcium phosphate and dicalcium phosphate have excellent biocompatibility and are well accepted by both hard tissue and soft tissue. The experimental results also indicated that dense hydroxyapatite is non-bioresorbable while other porous calcium phosphate ceramics are bioresorbable. FNT .sup.1 A bioactive glass material whose major components are CaO, SiO.sub.2 and P.sub.2 O.sub.5. Minor components may be Na.sub.2 O, MgO, Al.sub.2 O.sub.3, B.sub.2 O.sub.3 and CaF.sub.2. A bioactive glass can form a surface layer of hydroxyapatite when soaked in the aqueous environment.
The surgeon is most interested in implant materials that can be shaped and harden in situ, but such bioceramic preparations are not yet available. Most of the calcium phosphate ceramics for medical applications are prepared either in granule form or block form. The granule form has poor manipulation characteristics while the block form is very brittle and difficult to shape. In order to solve the above problems, many attempts have been made to prepare binder systems for bioceramics. Plaster of Paris, collagen, polylactate, polyacrylate, calcium phosphate grout and hydroxyapatite cement have been used.
Ideally, a useful binder system for bioceramics should have good biocompatibility, (including a near neutral pH), a suitable bioresorption rate, be moldable at surgical sites, and have good setting characteristics. The acidity of the setting cement is dependent on the type of calcium phosphate salt used, the acidity of the setting reagent, and the reaction rate. Typical cements are formed from dissolution and recrystallization of salts with Ca/P mole ratio&gt;1 after combination with acidic reagents.
When the calcium phosphate salt reacts with the acid setting reagent to form a cement, the calcium phosphate dissolves and new calcium compounds are formed during the setting stage. The extent of the reaction, the setting time and setting characteristics are sensitive to the nature of calcium phosphate powder, the pH and the type of setting reagents. Even when excess calcium phosphate powder is used to form a paste with highly soluble acidic setting reagent, the setting cement will nevertheless contain some unreacted acid setting reagent trapped in the cement. The result is a low surface pH of the setting cement. If the calcium phosphate cementing powder is near neutral and has a very slow dissolution rate, the surface pH will stay low for a long time. This low pH cement is undesirable since it may cause irritation and inflammatory reactions. Additionally setting times of this cement are difficult to control and it has poor manipulation characteristics.
Most binders have disadvantages. Plaster of Paris has a reasonable setting characteristics but the resorption rate is too fast. Collagen-hydroxyapatite composites and polylactatehydroxyapatite can serve as a useful delivery system for hydroxyapatite or other calcium phosphate granular ceramics, but these composite materials must be premolded; they cannot be molded at the surgical site.
Calcium phosphate grout does not set well in the in situ aqueous environment. For example, a recently reported calcium phosphate cement combined with bifunctional acids as setting reagents (U.S. Pat. No. 4,668,295) was very acidic, disintegrated very fast in the in situ aqueous environment, and lacked good setting characteristics. Pure hydroxyapatite cement prepared by reacting tetracalcium phosphate and other calcium phosphates is not resorbable and does not have good setting characteristics (U.S. Pat. Nos. 4,518,430 and 4,612,053).
Oonishi.sup.2 reported a bioactive .alpha.-tricalcium phosphate cement. This calcium phosphate cement has a reasonable setting time and strong mechanical strength, but is very acidic. More recently, a bioglass cement containing calcium phosphate using phosphoric acid or calcium hydroxide as the setting reagent has been reported..sup.3 The bioglass cement with phosphoric acid has low pH. No setting characteristic of this bioglass cement has been reported. FNT .sup.2 H. Oonishi, et al, "Studies on Development of .alpha.-TCP Bioactive Bone Cement" Posted Paper, Engineering Foundation Conferences, Bioceramics, Santa Barbara, Calif. 1986. FNT .sup.3 W. S. Chen, Y. Chen, J. P. Rausch, E. A. Monroe, "Phosphate Glass Bone Graft", page 241, The 15th Annual Meeting of the Society for Biomaterials, Apr. 28-May 2, 1989, Lake Buena Vista, Fla.